Pharmacophore Models of Paclitaxel- and Epothilone-Based Microtubule Stabilizing Agents

Lee, Sangbae,Lee, Yuno,Briggs, James M.,Lee, Keun Woo Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.7

Microtubules play an important role in intracellular transport, mobility, and particularly mitosis. Paclitaxel (Taxol$^{TM}$) and paclitaxel-like compounds have been shown to be anti-tumor agents useful for various human tumors. Paclitaxel-like compounds operate by stabilizing microtubules through interface binding at the interface between two ${\beta}$-tubulin monomers in adjacent protofilaments. In this paper we present the elucidation of the structural features of paclitaxel and paclitaxel-like compounds (e.g., epothilones) with microtubule stabilizing activities, and relate their activities to spatial and chemical features of the molecules. CATALYST program was used to generate three-dimensional quantitative structure activity relationships (3D-QSARs) resulting in 3D pharmacophore models of epothilone- and paclitaxel-derivatives. Pharmacophore models were generated from diverse conformers of these compounds resulting in a high correlation between experimental and predicted biological activities (r = 0.83 and 0.91 for epothilone and paclitaxel derivatives, respectively). On the basis of biological activities of the training sets, five- and four-feature pharmacophore hypotheses were generated in the epothilone and paclitaxel series. The validation of generated hypotheses was achieved by using twelve epothilones and ten paclitaxels, respectively, which are not in the training sets. The clustering (grouping) and merging techniques were used in order to supplement spatial restrictions of each of hypothesis and to develop more comprehensive models. This approach may be of use in developing novel inhibitor candidates as well as contributing a better understanding of structural characters of many compounds useful as anticancer agents targeting microtubules.

Pharmacophore Models of Paclitaxel- and Epothilone-Based Microtubule Stabilizing Agents

Sangbae Lee,이유노,James M. Briggs,이근우 대한화학회 2013 Bulletin of the Korean Chemical Society Vol.34 No.7

Microtubules play an important role in intracellular transport, mobility, and particularly mitosis. Paclitaxel (TaxolTM) and paclitaxel-like compounds have been shown to be anti-tumor agents useful for various human tumors. Paclitaxel-like compounds operate by stabilizing microtubules through interface binding at the interface between two β-tubulin monomers in adjacent protofilaments. In this paper we present the elucidation of the structural features of paclitaxel and paclitaxel-like compounds (e.g., epothilones) with microtubule stabilizing activities, and relate their activities to spatial and chemical features of the molecules. CATALYST program was used to generate three-dimensional quantitative structure activity relationships (3D-QSARs) resulting in 3D pharmacophore models of epothilone- and paclitaxel-derivatives. Pharmacophore models were generated from diverse conformers of these compounds resulting in a high correlation between experimental and predicted biological activities (r = 0.83 and 0.91 for epothilone and paclitaxel derivatives, respectively). On the basis of biological activities of the training sets, five- and four-feature pharmacophore hypotheses were generated in the epothilone and paclitaxel series. The validation of generated hypotheses was achieved by using twelve epothilones and ten paclitaxels, respectively, which are not in the training sets. The clustering (grouping) and merging techniques were used in order to supplement spatial restrictions of each of hypothesis and to develop more comprehensive models. This approach may be of use in developing novel inhibitor candidates as well as contributing a better understanding of structural characters of many compounds useful as anticancer agents targeting microtubules.

Association between Coaches` Social Network and Their Performance Outcome: Korean Olympic Soccer Team

( Sangbae Jun ),( Han J. Lee ),( Kyunghwa Lee ),( Narae Son ),( Juhyun Kwak ) 한국체육학회 2016 국제스포츠과학 학술대회 Vol.2016 No.1

Purpose: Coaches are presented with the opportunity to interact with their athletes as well as other coaches, which makes their social networks. Previous work (Burt, 1992) has found links between network positions and individual performance. We tested Burt’s (1992) theory using a Korean Olympic Soccer team. Coaches and their athletes are situated in the unique network where coaches are tied to athletes’ performance. There has been limited research examining the nature of these social networks with athletes and other coaches (Trudel and Gilbert 2004). Thus, the purpose of this study was to examine associations between the social networks and performance outcomes of Korea national soccer team coaches. Method: The study surveyed coaches’ social networks of Korea Olympic soccer team in the periods from 1992 to 2012. Their performance in the international games (e.g., the World Cups, the Olympics, Asian games, Asian Cups, FIFA-U20, and FIFA-U17) was measured using winning rate of career records. The data was analyzed with UCINET6 and NetDraw, and descriptive statistics for analyzing the relationships. Result: Findings of the study indicated Hong Myung-Bo and Huh Jung-Moo had the biggest and various social networks, and the highest scores in centrality measures. Homophily was found that most of head coaches and assistant coaches were graduates of Yonsei or Korea university. Findings did not show statistically significant relationship between coaches’ social network and their performance outcome. Conclusion: Evolution of coaches’ social networks and homophily had been discovered in a vast array of network studies were discussed.

S-58 H. pylori infection is associated with subclinical coronary atherosclerosis in healthy subjects

( Minyoung Lee ),( Haeri Baek ),( Jong Suk Park ),( Sohee Kim ),( Chanhee Kyung ),( Sangbae Lee ),( Jihong You ),( Su Jung Baik ),( Byoung Kwon Lee ),( Jie-hyun Kim ),( Chul Woo Ahn ),( Kyung Rae Kim 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1

Background/Aims: Helicobacter pylori (H. pylori) is a gastrointestinal pathogen known to be associated with cardiovascular disease (CVD). However, most reports about the effect of H. pylori on CVD were investigated in patients with a previous history of CVD and little is known in healthy subjects. We evaluated the association between H. pylori infection and subclinical atherosclerosis using cardiac multidetector computed tomography (MDCT) in healthy subjects without CVD history. Methods: From December 2007 to February 2014, 471 subjects who underwent all of rapid urease test (CLO test), pulse-wave velocity (PWV) and MDCT for health check-up were enrolled. H. pylori infection was defined by CLO test positivity on endoscopic gastric biopsy. Significant coronary artery stenosis was defined as ≥50% stenosis in any major epicardial coronary vessel on MDCT. Results: The CLO-positive subjects had a lower high density lipoprotein-cholesterol (HDL-cholesterol) level than the CLO-negative subjects. Although there was no difference in the mean value of PWV, the incidence of significant coronary stenosis was higher in CLO-positive group (7.9% versus 2.9%, p=0.01). Also, the number of subjects with coronary artery calcium score>0 and Log{(Number of segments with plaque)+1} were slightly higher in CLO-positive group. CLO-positive group was 3-fold more likely to have significant coronary artery stenosis even after adjusting confounding factors (adjusted OR 3.081, 95% confidence interval 1.169-8.119, p=0.02). Conclusions: In a healthy population, current H. pylori infection was associated with significant subclinical coronary artery stenosis. The causal effect of H. pylori on subclinical atherosclerosis in a ‘healthy’ population remains to be investigated further.

큐잉 이론에 의한 콤퓨터 통신망의 윈도우 흐름제어

이상례(Lee, sangrae),박민용(Park, Mignon),이상배(Lee, sangbae) 대한전자공학회 1986 대한전자공학회 학술대회 Vol.1986 No.12

A femtosecond pulse fiber laser at 1935 nm using a bulk-structured Bi2Te3 topological insulator.

Jung, Minwan,Lee, Junsu,Koo, Joonhoi,Park, Jaehyun,Song, Yong-Won,Lee, Kwanil,Lee, Sangbae,Lee, Ju Han Optical Society of America 2014 Optics express Vol.22 No.7

<P>We experimentally demonstrate a femtosecond mode-locked, all-fiberized laser that operates in the 2 μm region and that incorporates a saturable absorber based on a bulk-structured bismuth telluride (Bi(2)Te(3)) topological insulator (TI). Our fiberized saturable absorber was prepared by depositing a mechanically exfoliated, ~30 μm-thick Bi(2)Te(3) TI layer on a side-polished optical fiber platform. The bulk crystalline structure of the prepared Bi(2)Te(3) layer was confirmed by Raman and X-ray photoelectron spectroscopy measurements. The modulation depth of the prepared saturable absorber was measured to be ~20.6%. Using the saturable absorber, it is shown that stable, ultrafast pulses with a temporal width of ~795 fs could readily be generated at a wavelength of 1935 nm from a thulium/holmium co-doped fiber ring cavity. This experimental demonstration confirms that bulk structured, TI-based saturable absorbers can readily be used as an ultra-fast mode-locker for 2 μm lasers.</P>

LLC CLASS 3 알고리즘에 관한 연구

이길흥(KilHung Lee),유인태(InTae Yoo),박민용(Mignon Park),이상배(SangBae Lee) 대한전자공학회 1990 대한전자공학회 학술대회 Vol.1990 No.11

Characteristics and Cellular Behavior of Hydrolyzed Poly (ε-caprolactone)/Equine Bone 3D Printed Scaffold

( Sangbae Park ),( Kyoung-je Jang ),( Myungchul Lee ),( Jae Woon Lim ),( Jae Eun Kim ),( Jiyong Park ),( Hyun Mok Son ),( Jong Hoon Chung ) 한국농업기계학회 2019 한국농업기계학회 학술발표논문집 Vol.24 No.1

For the dental implant to support the functional load, adequate quality of alveolar bone is necessary. Alveolar bone defects make it difficult for a dental implant to be grafted and function. The 3D printed bioactive ceramic incorporated Poly(ε-caprolactone) (PCL) scaffolds hold great promise to be used as synthetic bone graft substitutes. However, 3D printed scaffolds still lack adequate surface properties for cells to be attached to it. In this study, Poly(ε-caprolactone)/Equine bone (PCL/EB) scaffolds were fabricated using microextrusion based 3D printing technique. PCL/EB scaffolds were then hydrolyzed using sodium hydroxide solution. The mechanical strength and the surface property of the hydrolyzed PCL/EB scaffolds were evaluated using a universal testing machine (UTM) and water contact angle analysis respectively. The in vitro behavior of the hydrolyzed PCL/EB scaffold was investigated using dental pulp stem cells (DPSCs). Cell proliferation and osteogenic differentiation of DPSCs on hydrolyzed PCL/EB scaffold were discussed using water soluble tetrazolium salt (WST-1) assay, Alizarin Red Staining (ARS), and Immunocytochemistry (ICC) method. The result of this study shows that hydrolyzed PCL/EB scaffold is a suitable candidate for regeneration of bone defect.

Enhanced Osteogenic Differentiation of Dental Pulp Stem Cells on Hydrolyzed Poly (ε-caprolactone)/Equine Bone 3D Printed Scaffold

( Sangbae Park ),( Kyoung-je Jang ),( Myungchul Lee ),( Jae Woon Lim ),( Jae Eun Kim ),( Jiyong Park ),( Hyun Mok Son ),( Jong Hoon Chung ) 한국농업기계학회 2019 한국농업기계학회 학술발표논문집 Vol.24 No.2

For the dental implant to support the functional load, adequate quality of alveolar bone is necessary. Alveolar bone defects make it difficult for a dental implant to be grafted and function. The 3D printed bioactive ceramic incorporated Poly(ε-caprolactone) (PCL) scaffolds hold great promise to be used as synthetic bone graft substitutes. However, 3D printed scaffolds still lack adequate surface properties for cells to be attached to it. In this study, Poly(ε-caprolactone)/Equine bone (PCL/EB) scaffolds were fabricated using microextrusion based 3D printing technique. PCL/EB scaffolds were then hydrolyzed using sodium hydroxide solution. The mechanical strength and the surface property of the hydrolyzed PCL/EB scaffolds were evaluated using a universal testing machine (UTM) and water contact angle analysis respectively. The in vitro behavior of the hydrolyzed PCL/EB scaffold was investigated using dental pulp stem cells (DPSCs). Cell proliferation of DPSCs on hydrolyzed PCL/EB scaffold was discussed using water soluble tetrazolium salt (WST-1) assay. And osteogenic differentiation of DPSCs on the scaffold was further investigated using Alizarin Red Staining (ARS), and western blot method. The result of this study shows that hydrolyzed PCL/EB scaffold is a suitable implant material for regeneration of bone defect.

Poly (ε-caprolactone)/Equine Bone Film for Guided Bone Regeneration

( Sangbae Park ),( Kyoung-je Jang ),( Myungchul Lee ),( Jae Woon Lim ),( Jae Eun Kim ),( Jong Hoon Chung ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.2

For the dental implant to support the functional load, adequate quality of alveolar bone is necessary. Alveolar bone defects make it difficult for a dental implant to be grafted and function. The guided bone regeneration is a surgical procedure that is mainly used to treat bone defects. Various barrier membranes such as titanium, polymer, and bioactive materials are used to prevent the formation of connective tissue into the defect site. In this study, Poly (ε-caprolactone)/Equine bone (PCL/EB) films were fabricated as a barrier membrane for guided bone regeneration. PCL/EB solution was prepared incorporating equine bone into 10% (w/v) PCL/acetone solution. The PCL/EB films were made by evaporating the solution on a flat plate. The surface property of the PCL/EB film was evaluated using Fourier transform infrared (FT-IR) and water contact angle analysis. The in vitro behavior of the PCL/EB film was investigated using dental pulp stem cells (DPSCs). Cell proliferation and osteogenic differentiation of DPSCs on PCL/EB film were discussed using water soluble tetrazolium salt (WST-1) assay, Alizarin Red Staining (ARS), Immunocytochemistry (ICC), and Western Blotting method. The result of this study shows that PCL/EB film is a suitable candidate for guided bone regeneration membrane.